The program is designed to investigate the basic mechanisms by which cellular electrolyte exchanges and renal transport processes maintain homeostatic control of electrolyte, water and acid-base balance of the body, and how these homeostatic processes are disrupted in a variety of clinical disorders. These problems will be approached from many different levels, using a wide variety of tools and techniques. Cellular electrolyte exchanges of H ion, K ion, and Na ion and the relation of these exchanges to transmembrane potential differences will be examined with direct tissue analysis, intracellular cation-sensitive microelectrodes, and isotopic fluxes. Basic problems in renal physiology concerning the mechanism and control of tubular transport of Na ion K ion, Ca ions, PO4, uric acid on H20 will be investigated by micropuncture and microperfusion techniques in rats and dogs. The physiologic, pathologic and pharmacologic factors influencing the renal excretion of electrolytes and water will be studied by modified clearance techniques in dogs and rats. Patients with a variety of clinical disorders will be studied both by clearance and metabolic balance techniques, and where appropriate the results of functional studies will be correlated with morphologic changes observed by renal biopsy. Finally, in situations where it is possible, the clinical disorders will be simulated by experimental disease models in dogs and/or rats, thus permitting more intricate dissection of the pathophysiologic processes.